The
'804 and the '016 patents are directed towards
topical suspension formulations containing ciprofloxacin and
dexamethasone. Whereas, the '805 patent is directed
towards methods of treating middle ear infections using
aqueous suspension formulations containing ciprofloxacin and
dexamethasone. Ciprodex®, a brand name
pharmaceutical drug for treating middle ear infections
(otitis media) in children with ear tubes, as well as outer
ear infections (otitis externa) in children and adults,
includes ciprofloxacin and dexamethasone as the active
ingredients.

In
order to market and sell Ciprodex®, Alcon
listed the Patents-in-Suit in the Food and Drug
Association's (“FDA”) Approved Drug Products
with Therapeutic Equivalence Applications, commonly known as
the Orange Book. See 21 U.S.C. § 355(B)(1).
Thereafter, Defendants filed an Abbreviated New Drug
Application (“ANDA”) with the FDA in order to
seek approval to market a generic version of
Ciprodex®. See 21 U.S.C. §
355(j)(1). Accordingly, pursuant to 21 U.S.C. §
355(j)(5)(B)(iii), Alcon initiated this suit against
Defendants because Defendants' request to market the
generic version of Ciprodex® is done prior to
the expiration of the Patents-in-Suit.

On
February 23, 2017, a stipulation and order staying the
litigation between Plaintiffs and Defendant Watson was
entered on the record. (See D.I. 100) Thereafter, on
April 3, 2017, another stipulation and order was entered on
the record between Plaintiffs and Defendant Par regarding
Par's ANDA filings constituting an act of infringement of
the '805 patent, and that Par will not assert any defense
of non-infringement as to the '805 patent in this suit.
(See D.I. 114)

As
such, the remaining disputed claim terms between Plaintiffs
and Defendant DRL include-“A topically administrable
suspension composition intended for application to the eye,
ear or nose, ” as recited in claim 1 of the '804
patent; “A topically administrable aqueous suspension
composition intended for application to the eye, ear or nose,
” as recited in claims 1, 2 and 3 of the '016
patent; and “Treating a Human Patient, ” as
recited in claim 1 of the '805 patent.

On May
8, 2017, pursuant to L. Pat. R. 4.6, a Markman
hearing was conducted before the Court for the aforementioned
terms. These terms are construed below.

BACKGROUND

Ciprodex®
is an FDA approved pharmaceutical product that includes two
active ingredients-ciproflaxcin and dexamethasone.
Ciprofloxacin is an antibiotic that treats infections caused
by bacteria. And, dexamethasone is a steroid that reduces the
actions of chemicals in the body that cause inflammation.

I.
The Patent Family

The
Patents-In-Suit include the '804 patent, the '016
patent and the '805 patent. The '016 patent is a
continuation[1] of the '804 patent, and as such shares
the same specification and inventive entity as the '804
patent. Both, the '804 and the '016 patents, are
directed towards suspension formulations containing
dexamethasone and ciprofloxacin. The formulation contains a
nonionic polymer, a nonionic surfactant and an ionic tonicity
agent. The formulations are physically stable and easily
re-suspended, and are intended for topical application to the
eye, ear or nose. (See Abstract of the '804
patent and the '016 patent).

The
only difference between the '804 patent and the '016
patent is the claimed subject matter. The '804 patent
includes one (1) claim directed to a composition that is
intended for application to the eye, ear or nose. Whereas,
the '016 patent includes five (5) claims, wherein claims
1, 2 and 3 are in independent form, and claims 4 and 5 depend
from claim 3.

The
'804 and the '016 patents disclose a formulation that
comprises two active agents- corticosteroids (dexamethasone)
and antibiotic (ciprofloxacin). (See the '804
patent[2], col. 2, ll. 1 5) Dexmathasone can be
present in any ophthalmic or optically acceptable form having
poor water solubility such that the resulting formulation is
a suspension formulation. Whereas, ciprofloxacin can also be
present in any ophthalmic or optically acceptable form such
that the ciprofloxacin ingredient is in solution in the final
formulation. (See Id. at col. 2, ll. 10-20) In
addition to these aforementioned active ingredients, the
suspension formulations also contain-sodium chloride as an
ionic tonicity agent, a nonionic polymer, a nonionic
surfactant, a quaternary ammonium halide as a preservative, a
chelating agent, and boric acid. (See Id. at col. 2,
ll. 30-col. 3, ll. 11) The resultant suspension formulation
has a desired pH of 4.5 and an average particle (mean volume
basis) of the dexamethasone ingredient to be less than 10
µm (micro-meters) to avoid irritation or discomfort to
the user. (See Id. at col. 3, ll. 10-25)

The
'804 patent discloses the different methods of forming
this suspension formulation; and the different formulations
A-E that were tested for resuspension time in accelerated and
realtime settling studies. (See Id. at col. 4) The
result of these studies illustrated that the suspension
formulation can be preserved such that it meets both the
United States Pharmacopeia (USP) and the European Pharmacopia
(Ph. Eur.) minimum preservative requirements for ophthalmic
and otic formulations. (See Id. at col. 6, ll.
25-30)

With
respect to the '805 patent, issued on August 2, 2016, it
is a separate and distinct patent from the '804 patent
and the '016 patent because the '805 patent is not a
continuation, divisional or a continuation-in-part
application of either the '804 patent or the '016
patent. As such, the '805 patent does not share the same
disclosure as the '804 and the '016 patents. The
earliest priority date of the '805 patent potentially
dates back to September 21, 2001, from provisional
application number 60/323, 951. (See Front Cover of
the '805 patent)

The
'805 patent is directed towards method of treating middle
ear infections in humans having an open tympanic
membrane[3] by using aqueous suspension formulations,
which contain dexamethasone and ciprofloxacin. (See
Abstract of the '805 patent)

The
method of treatment includes topical application of a fixed
combination of ciprofloxacin and dexamethasone as an adequate
suspension product. Generally, the dosage regimen includes
applying the suspension product twice a day. Each application
involving administering three or four drops into the ear
canal, and preferably pumping the tragus[4] to force product
through the opening in the tympanic membrane, and in effect
to the site of the infection/inflammation in the middle ear.
(See the '805 patent, col. 2, ll. 20-30)

The
'805 patent discloses that in addition to the active
agents-ciprofloxacin and dexamethasone-the suspension
formulations include a tonicity agent. The tonicity agent may
be ionic (e.g., NaCl) or nonionic (e.g., mannitol); however,
NaCl is preferred as the tonicity agent. (Id. at
col. 3, ll. 25-33)

Studies
of Ciprodex® were conducted on pediatric
patients with acute otitis media with tympanostomy tubes. The
studies indicated that this drug, which was administered
twice a day in pediatric patients, was safe and tolerated
well. (Id. at col. 15, ll. 15-20) The '805
patent includes twenty-two (22) claims, wherein claim 1 is an
independent claim. Claim 1 is a method claim for treating a
human patient, which includes the steps of-(i) diagnosing the
patient having otitis media and an open tympanic membrane,
and (ii) topically applying into the ear canal of the
patients ear an aqueous suspension composition. (Id.
at col. 15, ll. 50-62)

Dr.
Crowley, on behalf of Alcon, has provided opinion concerning
the meaning of certain claim terms in the Patents-in-Suit.
(See Declaration of Crowley (“Decl. of
Crowley”) at ¶ 1; D.I. 54-9). Dr. Crowley notes
that the preamble[5] of the '804 patent, a term in dispute,
which includes the term “suspension composition”
means a liquid formulation in which one or more active
ingredients are in suspension. (Id. at ¶ 44).
That is, without the active ingredients being in suspension,
no person skilled in the art would refer to a formulation as
a “suspension composition.” (Id.)

With
regards to “suspension”, Dr. Crowley notes that
in chemistry, a suspension is defined as a two-phase system
in which an un-dissolved compound is dispersed in a solid,
liquid or a gas vehicle. In pharmaceuticals, Dr. Crowley
notes, this term refers to solid particles that are dispersed
within a liquid vehicle, which is generally water.
(Id. at ¶ 13) Dr. Crowley notes that the
suspension formulation must meet chemical and physical
stability requirements sufficient to justify shelf life.
Stability being defined as “the extent to which a
product retains, within specified limits, and throughout its
period of storage and use (i.e., its shelf life)
[…].” (Id. at ¶ 14, citing
United States Pharmacopeia (23rd edition
1995) (“1995 USP”)) Most pharmaceutical products
have a shelf life of at least two (2) years. (Id. at
¶ 15)

A
physical stability of a suspension formulation refers to the
stability of the physical aspects of the composition,
including-appearance, pH, viscosity, dissolution and particle
size distribution for undissolved components. The size
distribution of undissolved particles must remain the same
for the shelf life of the suspension. (Id. at ¶
16) A pharmaceutical suspension is acceptable even if it
settles during its shelf life, so long as it is easily
re-suspendible and homogeneous for a long duration to
administer a uniform dose. (Id. at ¶ 17)

Conversely,
the composition would be unacceptable if over time, the
particles start to clump together and settle in a loose
structure, or form a dense sediment on the bottom of the
container, known as “caking.” (Id. at
¶ 18) Dr. Crowley notes that this is unacceptable as it
prevents an administration of a uniform dose of the active
ingredient and reduces the potential shelf-life of the
suspension formulation. (Id. at ¶ 19) As such,
absent such physical stability and easily re-dispersibility,
the FDA would not have approved this drug. (Id. at
¶ 21)

Regarding
the preamble of the '804, Dr. Lawrence notes that one
skilled in the art would recognize that the asserted claims
recite a list of specific ingredients with specific
proportions, which includes pharmaceutical ingredients with
pharmaceutical excipients. (See Decl. of Lawrence at
¶ 70) Further, Dr. Lawrence notes that the preamble of
the'804-does not give additional meaning to the
pharmaceutical compositions, does not add any structure to
the claimed invention, and one could omit reading the
preamble and still have the same complete understanding of
the pharmaceutical compositions. (Id. at ¶ 72)
Dr. Lawrence cautions that Actavis' proposed addition of
“with at least one active ingredient in
suspension” to the preamble is redundant and misleading
because one skilled in the art would recognize that the
particular claimed compositions are directed to two specific
drugs-dexamethasone and ciprofloxacin-and not at least one
active ingredient in suspension. (Id. at ¶ 77)

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Lastly,
Dr. Soham Roy, on behalf of Alcon, provides his opinion on
the disputed claim term &ldquo;treating a human
patient&rdquo; as recited in the preamble of claim 1 of the
&#39;805 patent. (Declaration of Dr. Soham Roy (&ldquo;Decl.
of Roy&rdquo;) at &para; 1; D.I. 94) Dr. Roy notes that the
term &ldquo;treating&rdquo; in the aforementioned claim term
includes an intent requirement, such that the
composition must be administered or the procedure must be
performed with an intent to cause a therapeutic benefit in
the subject. (See Decl. of Roy at &para; 21) In
other words, &ldquo;treating a human patient&rdquo; is
directed towards a procedure that the composition must be
performed &lsquo;for the purpose&#39; of effecting a
therapeutic improvement in the patient. (Id. at
¶ 25) Dr. Roy further states, ...

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